Spinal anesthetic solution



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Patented Nov. 22, 19 32 UNITED 'STATES PATENT OFFIE GEORGE PHIII'OIPI'I'KIN, OF BERGENFIELD, NEW JERSEY, AND CHARLES WARREN HOOPEB, OFJAMAICA, YORK, ASSIGNOBS TO B. A. METZ LABORATORIES INC,

OF NEW YORK, N.-Y., A CORPORATION OF NEW YORK SPINAL ANESTHETIO SOLUTION80 Drawing.

larly to spinal anaesthetic solutions which have as a base an alkamineester of an aromatic acid adapted for use as a spinal anaesthetic agentsuch as the monohydrochloride of paraamino benzoyl-diethyl-amino-ethanolwhich is generally known as Novocaine or Procaine. One of its objects isto provide a solution which does not mix with the spinal fluid-whenemployed clinically for the production of spinal anaesthesia until theanaesthetic agent has been absorbed, thereby regulating the time, extentand intensity of anaesthesia. Further and more specific objects,features and advantages will more clearly appear from the detaileddescription given below.

Spinal anaesthesia (sometimes called spinal analgesia) is a method ofanaesthesia used extensively for surgical operations below thediaphragm. It is produced by injecting a solution of a spinalanaesthetic agent directly into the spinal fluid contained in thesubarachnoid space of the spinal canal. The injection is made throughone of the vertebral interspaces of the lower dorsal or lumbar region ofthe spine.

Thespinal anaesthetic solutions as heretofore employed by diflerentsurgeons are pre pared by dissolving the spinal anaesthetic agent in aVehicle such as water, physiological salt solution, spinal fluid ordilute alcohol solution; the purpose being to produce a fluid of thesame, heavier or lighter specific gravity compared with the spinalfluid.

A great objection to the spinal anaesthetic solutions hitherto used isthe absolute commitment of the surgeon to the consequences of thesesolutions when injected into the spinal fluid. Once injectedthe'anaesthetic solution mixes with the spinal fluid and as a result itsaction cannot be controlled by the surgeon. Despite all precautions theanaesthetic solution may rapidly disseminate through the spinal fluidtowards the brain and produce untoward symptoms such as pallor bloodpressure and at times even death rom paralysis of the nerves controllingrespiration.

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Application filed Iay 10, 1928. Serial No. 276,804.

In addition there is also uncertainty as to the time, extent andintensity of anaesthesia due to dilution of the spinal anaestheticsolution by the spinal fluid and not infrequently the anaesthesia wearsoff before the operation is completed.

In order to revent uncertainty as to the extent of anaest esia, tostabilize the intensity and to regulate the time ofanaesthesia, todiminish' the tremendous drop in blood ressure and to prevent nausea andvomiting, we have devised a spinal anaesthetic solution that will notmix wlth the spinal fluid until the spinal anaesthetic agent has beenabsorbed by the intradural nerve trunks and nerve roots. The spinalanaesthetic solution has the additional characteristic that it floats inthe spinal fluid, not. unlike the air bubble in a spirit level, and as aresult, anzesthesiacan be roduced higher or lower on the justing theposition of the patient. Also, accor'ding to our improvements, a spinalanaesthetic solution is roduced which is stable and sterile and may keptfor long periods of time as a ready-to-use solution.

To ascertain the intradural action of our sur ace as the surgeon desiresby merely spinal anaesthetic solution as compared with 3 same. As afinal check, methylene-bluewas added to the various anaestheticsolutions and injected directly into the spinal fluid in thesubarachnoid space of the spinal canal. Postanaesthetic taps were thenmade at definite intervalsand theextent and amount of dissemination wasdetermined by the use of a colorimeter. v

We have discovered that stable controllable anaesthetic solutions can beproduced by including therein a gluelike adhesive substance preferablyin the nature of gliadin dissolved in alcohol which so affects thespinal anaesthetic solution as to increase its viscosity and not inhibitthe absorption of the spinal anaesthetic agent. The gliadin is insolublein spinal fluid and precipitates on contact with spinal fluid forming asemipermeable membrane between the spinal anaesthetic solution and thespinal fluid. When we refer to gliadin or a solution of gliadin it willbe understood that this includes the alcohol-soluble protein found inmost of the cereals such as wheat, rye, maize, etc. For the spinalanaesthetic agent we prefer to use the monohydrochloride ofpara-amino-benzoyldiethyl-amino-ethanol (novocaine or procaine).However, other alkamine esters of aromatic acids adapted for use asspinal anaesthetic agents may be employed, for example the hydrochlorideof diethyl-amino-propylcinnamate (apothesine) and the hydrochloride ofara-amino-benzoyl-dimethyl-aminomethyl-isobutanol (tutocaine) Inproducing the spinal anaesthetic solution the proportions may be greatlyvaried depending upon the various conditions to be met, etc., but weprefer solutions in which the monohydrochloride ofpara-amino-benzoyl-diethyl-amino-ethanol varies from 5% to 10%, g'liadinfrom 0.03% to 0.06% and ethyl alcohol from 10% to 16%. The alcohol isadded to hold the gliadin in solution and to lower specific gravity.

Good results have been obtained withsolutions prepared as follows: (1)monohydrochloride of para-amino-benzoyl-diethyl-aminc-ethanol 10 grams,wheat gliadin 0.06 gram, absolute ethyl alcohol 16 cubic centimeters anddistilled water in suflicient quantity to make 100 cubic centimeters.The doses to be applied averages about 2 cubic centimeters of thissolution; (2) monohydrochloride ofpara-amino-benzoyl-diethyl-aminoethanol 5 grams, wheat gliadin 0.03gram, absolute ethyl alcohol 10 cubic centimeters and distilled water insuficient quantity to make 100 cubic centimeters.

llnstead of the monohydrochloride one may use the free base, although wepreferto use the monohydrochloride.

The ingredients of the solution are preferably combined in the followingmanner.

The monohydrochloride of para-aminohenzoyl-diethyl-amino-ethanol isdissolved in 20 cubic centimeters of distilled water. The alcohol isconverted into a alcohol solution by the addition ofsuficient distilledwater. The gliadin is then dissolved in the cohol solution and then themonohydrochloride of para-amino-benzoyl-diethyl-aminoethanol solution isadded and thoroughly ed. A scient quantity of distilled Leaaeea water isfinally added to make cubic centimeters.

We have also obtained good results by adding cereal mucilages to thespinal anaesthetic solution as we have found that cereal mucilagesprepared from cereals containing gliadin, or their flours, by boilin inwater contain suflicient gliadin suspen ed or adsorbed by the starch toprevent dissemination of the spinal anaesthetic solution when iniectedinto the spinal fluid. The mucilage may be conveniently prepared byplacing 15 to 20 grams of wheat flour in a gauze bag and then suspendinthe bag containing the wheat flour in 200 cu ic centimeters of boilingdistilled water for a period of three hours.

The addition of 3 cubic centimeters to 6 cubic centimeters of the clearsupernatant mucilage to replace half of the gliadin or the addition of 5cubic centimeters to 10 cubic centimeters of the clear supernatantmucilage instead of the gliadin included in the above example has beenfound sufficient for each 100 cubic centimeters of the spinalanaesthetic We have also found that when solution. cereal mucilage isemployed instead of the gliadin the alcohol may be omitted.

In order to prevent infection of the s inal fluid it is essential thatthe spinal anaest etic solutions be sterile. sterility may be insured byfilling glass ampules of the desired volume with the freshly preparedsolution, then promptly sealing ofl the ampules with the aid of ablow-pipe and then submerging the ampules in boiling water 4 for 15 to30 minutes on three successive days or autoclaving them in a live steamsterilizer for 20 minutes at'15 pounds steam pressure. This procedurehas been found most practical because it prevents any loss byevaporation and also any accidental contamination after sterilization.

We have thoroughly tested these spinal anaesthetic solutions forsterility and stability. Relatively old ampules thereof have shown nochange in color and have retained their full anaesthetic potency. By ourimprovements, we are able to produce ready-touse spinal anaestheticsolutions which are far superior to the spinal anaesthetic solutionsheretofore employed and which do not mix with the spinal fluid whenemployed clinically until the spinal anaesthetic agent has beenabsorbed, thereby regulating the time, extent and intensity ofanaesthesia.

While we have described our improvements in great detail and withrespect to preferred forms thereof, we do not desire to be limited Wehave found that' lit to such details or forms sincemany modificaaw tionsand changes may be made and the invention embodied in widely differentforms without departing from the spirit or scope of the invention in itsbroader aspects. Hence we desire to cover all modifications and. fee

coming within the scope or language of any one or more of the appendedclaims.

We claim:

1. A new composition of matter comprising a spinal anaesthetic agent anda gluelike adhesive substance which is insoluble in the spinal fluid.

2. A new composition of matter comprising a spinal anaesthetic agent andgliadin.

3. A new composition of matter comprising a salt ofpara-amino-benzoyl-diethylamino-ethanol and a gluelike adhesivesubstance which is insoluble in the spinal fluid.

4. A new composition of matter comprising the monohydrochloride ofpara-amino- .benzoyl-diethyl-amino-ethanol and gliadin.

. 5. A new composition of matter consisting of 5% to 10% of themonohydrochloride of para-amino-benzoyl diethyl amino -ethanol, 0.03% to0.06% of gliadin and 10% to 16% of ethyl alcohol, the residue beingdistilled water.

6. As a new composition of matter a solution of 10 grams of themonohydrochloride of para-amino benzoyl diethyl amino ethanol and 0.06gram of Wheat gliadin in a mixture of 16 cubic centimeters of ethylalcohol and distilled water in sufficient quantity to make cubiccentimeters.

7. A new composition of matter com rising a spinal anaesthetic agent andwheat our mucilage.

8. A new composition of matter comprising the monohydrochloride ofpara-amino-benzoyl-diethyl-amino-ethanol and wheat flour mucilage.

9. A new composition of matter consisting of 5% to 10% of the'monohydrochloride of para-amino-benzoyl-diethyl amino ethanol, 5% to10% of wheat flour mucilage and 10% to 16% of ethyl alcohol, the residuebeing distilled water.

In testimony whereof, we afii'x our signatures.

GEORGE P. PITKIN, M. D. CHARLES W. HOOPER, M. D.

